CA9 expression is associated with neoplastic growth and has been correlated with prognosis in cancers of the brain, lung, breast, cervix, kidney, gastrointestinal track, and head and neck (1-6). CA9 is expressed in response to decreases in oxygen tension (7). This is believed to be an adaptive response that results in increased delivery of oxygen and nutrients to the tumor and may favor disease progression and eventual metastasis of cancer cells. CA9 expression is increased in many solid malignancies, with greatest expression in tumor cells immediately adjacent to areas of necrosis (1, 7). CA9 is also a marker for hypoxia in normal cells and most malignancies. In all malignancies where CA9 has been reported as a prognostic biomarker, with the exception of clear cell renal cell carcinoma (RCC), increased CA9 expression predicted a worse prognosis (1-4, 6). Expression in other normal tissue is limited to basal cells of hair follicles, gonadal epithelium, choroid plexus, and some gastrointestinal mucosa (8). However, in clear cell RCC, CA9 expression is not regulated by oxygen tension. CA9 is present in over 80% of primary and metastatic RCC, and CA9 is present in 95-100% of the clear cell variant, the most common histologic type of RCC. CA9 is not expressed in normal renal tissue (8, 9). For clear cell RCC, CA9 appears to be an excellent biomarker that establishes diagnosis, determines prognosis, predicts treatment response, and serves as a target for therapy. In particular, high CA9 expression is an independent predictor of longer disease-specific survival in patients with metastatic RCC (5, 10), and improved survival in patients with localized RCC (11, 12). However, despite widespread interest in CA9 and better understanding of the molecular defect leading to CA9 overexpression in clear cell RCC, the mechanism linking CA9 expression to improved prognosis and treatment response in RCC patients, while being an indicator of an otherwise poor prognosis is not understood. Therefore, there is a need to develop methods and compositions employing CA9 for use as a therapeutic agent.